Andrew W. Knott

EGF receptor signaling affects bcl-2 family gene expression and apoptosis after massive small bowel resection ☆

BACKGROUND After massive small bowel resection (SBR), enterocyte apoptosis is elevated and inversely correlates with epidermal growth factor receptor (EGFR) signaling. The purpose of the current study was to determine whether EGFR manipulation affects the expression of specific bcl-2 family members. METHODS A 50% proximal SBR or sham operation was performed in 3 groups of mice control, after exogenous EGF, or mutant mice with defective EGFR signaling (waved-2). Apoptotic index (no. of apoptotic bodies per crypt), and bax (pro-apoptosis) and bcl-w (anti-apoptosis) protein expression was measured in the remnant ileum after 12, 24, and 72 hours. RESULTS Waved-2 mice with defective EGFR showed the greatest increase in apoptosis and altered the ratio of bax to bcl-w in favor of apoptosis after SBR. Conversely, EGF prevented the expected increase in apoptosis after SBR by shifting the ratio of bax to bcl-w in favor of cell survival. CONCLUSIONS After massive small bowel resection, inhibition of the EGFR accelerates the rate of apoptosis and modifies the expression of specific bcl-2 family members to favor apoptosis. These results further support a specific mechanistic pathway for the regulation of enterocyte apoptosis after SBR via EGFR signaling.

Characterization of small bowel resection and intestinal adaptation in germ-free rats.

BACKGROUND After massive small bowel resection (SBR), the remnant bowel adapts by increasing enterocyte proliferation and apoptosis. The purpose of this study was to investigate the relevance of luminal bacteria on postresection intestinal cell turnover. METHODS Male germ-free (GF) and normally colonized control rats underwent either a 75% mid-SBR or sham operation. In other experiments, normally colonized control rats were given antibiotics in the drinking water. After 7 days, the remnant ileum was harvested and adaptation verified by alterations in wet weight, crypt depth, and villus height. Proliferation and apoptosis were measured in crypts as the percent of crypt cells staining for Ki-67 or the number of apoptotic bodies per crypt. RESULTS Both GF and control rats demonstrated significant increases in all adaptive parameters. Proliferation was increased after SBR in both groups, but significantly greater in the GF animals over control. This response could not be recapitulated after antibiotic treatment. Apoptosis increased equally after SBR in all groups. CONCLUSION Resection-induced intestinal adaptation occurs normally in GF animals. Epithelial-microbial interactions are probably not involved in the activation of enterocyte apoptosis. The germ-free studies offer the possibility that luminal bacteria may attenuate the proliferative response of the enterocyte to massive small bowel resection.

A serum factor(s) after small bowel resection induces intestinal epithelial cell proliferation: effects of timing, site, and extent of resection☆

BACKGROUND/PURPOSE After small bowel resection (SBR), serum induces proliferation in rat intestinal epithelial cells (RIEC-6). This study was designed to elucidate the effects of postoperative time interval, site, and magnitude of SBR on RIEC-6 proliferation. METHODS Serum was collected from rats at various times after a 75% mid-SBR or sham operation and added to RIEC-6 cells and growth determined over 5 days. In other experiments, cell growth was recorded in the presence of serum from rats after 25%, 50%, or 75% SBR, or after jejunal or ileal SBR. RESULTS SBR serum enhanced RIEC-6 cell proliferation as early as 12 hours after resection. The extent of SBR directly correlated with the level of adaptation; however, the effects on cell growth by the serum were similar. SBR serum induced proliferation equally after either proximal or distal resection. CONCLUSIONS Serum contains a factor that stimulates intestinal cell proliferation soon after SBR but independent of the degree or site of intestinal resection. Although humoral factor(s) play a role in the early induction of enterocyte proliferation after SBR, further modulation of adaptation to varied lengths or sites of intestinal resection are probably governed by mechanisms independent of factors that circulate in the serum.

Reoperative Venous Access

The maintenance of long-term venous access is critical to the livelihood of children in a variety of clinical situations, especially those who are dependent on parenteral nutrition. Whereas the traditional routes of either peripheral or central venous access are initially adequate, most of these sites eventually succumb to the pitfalls associated with long-term venous access. This review provides a comprehensive and multidisciplinary approach to the management of reoperative venous access with regard to preoperative planning and imaging and specific techniques in interventional radiology and surgery.